Effects of a TAML catalyst on mice exposed during pregnancy and lactation.

Tetra-amido macrocyclic ligands (TAMLs) are catalysts designed to mimic endogenous peroxidases that can degrade pollutants. Before TAMLs gain widespread use, it is first important to determine if they have endocrine disrupting properties. In this study, we evaluated the effects of the iron TAML, NT7, on hormone-sensitive outcomes in mice exposed during pregnancy and lactation, and on their litters prior to weaning. We administered NT7 at one of three doses to mice via drinking water prior to and then throughout pregnancy and lactation. Two hormonally active pharmaceuticals, ethinyl estradiol (EE2) and flutamide (FLUT), a known estrogen receptor agonist and androgen receptor antagonist, respectively, were also included. In the females, we measured pre- and post-parturition weight, length of pregnancy, organ weights at necropsy, and morphology of the mammary gland at the end of the lactational period. We also quantified maternal behaviors at three stages of lactation. For the offspring, we measured litter size, litter weights, and the achievement of other developmental milestones. We observed only one statistically significant effect of NT7, a decrease in the percentage of pups with ear opening at postnatal day 5. This contrasts with the numerous effects of EE2 on both the mother and the litter, as well as several modest effects of FLUT. The approach taken in this study could provide guidance for future studies that aim to evaluate novel compounds for endocrine disrupting properties.

Semen Protein CRISP3 Promotes Reproductive Performance of Boars through Immunomodulation.

Semen proteins play an important role in male reproductive performance and sperm fertilization ability and can be used as potential biomarkers to evaluate male fertility. The role of cysteine-rich secretory protein 3 (CRISP3) in male reproduction remains unknown. This study aimed to investigate the role of CRISP3 in the reproductive performance of boars. Our results showed that the CRISP3 protein content was significantly and positively correlated with boar fertility, sow delivery rate, and litter size. CRISP3 is highly expressed in the bulbourethral gland of adult boars and is enriched in the seminal plasma. It is localized in the post-acrosomal region of the sperm head and migrates to the anterior end of the tail after capacitation. The CRISP3 recombinant protein did not affect sperm motility and cleavage rate, but it significantly downregulated the mRNA expression of inflammatory factors IL-α, IL-1ß, and IL-6 and the protein expression of IL-α and IL-6 in lipopolysaccharide (LPS)-induced RAW264.7 cells, indicating that CRISP3 has an immunomodulatory function. In conclusion, our study suggests that semen CRISP3 protein levels positively correlate with reproductive performance, which may be achieved by regulating immune responses in the female reproductive tract.

Lactation body condition loss impaired conceptus development and plasma progesterone concentration at day 8 post-ovulation in primiparous sows.

The current study investigated effects of dietary amino acid (AA) availability on lactational body condition loss and metabolic status, in relation to reproductive parameters after weaning up to Day 8 post-ovulation. Primiparous sows (n = 35) were allocated to one of two lactation diets containing either low crude protein (CP, 140 g/kg) with a low percentage (8%) of slow protein in total protein (LL, n = 18) or high CP (180 g/kg) with a high (16%) percentage of slow protein (HH, n = 17). The HH diet was expected to improve AA utilization by supplying more AA, in a more gradual fashion. The diets did not affect sow body condition loss during lactation, while the HH diet tended to increase litter weight gain during the week 3 of lactation (Δ = 1.3 kg, P = 0.09). On Day 14 post-farrowing, HH diet led to higher plasma urea both pre-feeding and post-feeding (Δ = 2.3 mmol/L, P < 0.01, Δ = 2.4 mmol/L, P < 0.01, respectively), whilst plasma creatinine, NEFA and IGF-1 were similar. No dietary effects on reproductive parameters were found, however several relationships were found between body condition and reproductive parameters. Sows with higher body weight on Day 1 or Day 21 post-farrowing had greater follicle size on Day 3 post-weaning (ß = 0.03 mm/kg, P < 0.01, ß = 0.04 mm/kg, P < 0.01, respectively). At Day 8 post-ovulation, plasma progesterone concentration was negatively related to loin muscle loss (ß = -0.67 ng/ml · mm-1, P = 0.02), backfat loss (ß = -2.33 ng/ml · mm-1, P = 0.02), and estimated body fat loss (ß = -0.67 ng/ml · mm-1, P = 0.02). Both plasma progesterone and the number of corpora lutea were positively related to the energy balance during lactation (ß = 0.03 ng/ml · ME MJ-1, P = 0.01, ß = 0.01 CL/ME MJ, P = 0.02, respectively). The conceptus size at Day 8 post-ovulation was negatively related to body weight loss (ß = -0.01 mm/kg, P = 0.01), estimated body fat loss (ß = -0.02 mm/kg, P = 0.03) and estimated body protein loss (ß = -0.06 mm/kg, P = 0.04), and was positively related to the energy balance during lactation (ß = 5.2*10-4 mm/ME MJ, P = 0.01). In conclusion, body protein and fat losses during lactation reduced subsequent plasma progesterone concentration and conceptus development at Day 8 post-ovulation.

Impact of litter size on the hematological and iron status of gilts, sows and newborn piglets: a comparative study of domestic pigs and wild boars.

BACKGROUND: The critically low hepatic iron stores of newborn piglets are considered to be a major cause of neonatal iron deficiency in modern breeds of domestic pig (Sus domestica). The main factor believed to contribute to this phenomenon is large litter size, which has been an objective of selective breeding of pigs for decades. As consequence, iron transferred from the pregnant sow has to be distributed among a greater number of fetuses. RESULTS: Here, we investigated whether litter size influences red blood cell (RBC) indices and iron parameters in Polish Large White (PLW) piglets and gilts. Small and large litters were produced by the transfer of different numbers of embryos, derived from the same superovulated donor females, to recipient gilts. Piglets from large litters obtained following routine artificial insemination were also examined. Our results clearly demonstrated that varying the number of piglets in a litter did not affect the RBC and iron status of 1-day-old piglets, with all showing iron deficiency anemia. In contrast, gilts with small litters displayed higher RBC and iron parameters compared to mothers with large litters. A comparative analysis of the RBC status of wild boars (having less than half as many piglets per litter as domestic pigs) and PLW pigs, demonstrated higher RBC count, hemoglobin level and hematocrit value of both wild boar sows and piglets, even compared to small-litter PLW animals. CONCLUSIONS: These findings provide evidence that RBC and iron status in newborn PLW piglets are not primarily determined by litter size, and indicate the need to study the efficiency of iron transport across the placenta in domestic pig and wild boar females.

Effect of vitamin E, D-limonene, and their combination on nulliparous rabbit reproductive performance.

Oxidative status is important in reproductive performance and using two natural antioxidants is more beneficial than one in nulliparous rabbits. The goal, effect of vitamin E (VitE), D-limonene (DL), and VitE+DL on maternal LBW (MLBW), conception (CR), pregnancy (PR), and kindling rates (KR), gestation length (GL), total litter size at birth (TLSB) and weaning (TLSW), live kits at birth (LKB) and weaning (LKW), dead kits at birth (DKB) and weaning (DKW), kits mortality rate at weaning (KMRW), Kit weight at birth (KWB) and weaning (KWW), total kit weight at birth (TKWB) and weaning (TKWW), and concentrations of progesterone (P4) and Malondialdehyde (MDA), during first two pregnancies. A total of 24 healthy female WNZ rabbits were randomly selected and assigned into four groups (6/each). Control (animals injected with 1.0 mL propylene glycol), VitE (60 mg IM injection/animal, 2X/week pre-mating and 3X post-mating until mid-pregnancy, DL (20 mg IM injection/animal, 2X/week pre-mating and 1X at mating, and VitE+DL (IM injection/animal with the same doses and times applied in VitE and DL groups. All animals were treated during 1st pregnancy only. The results confirmed that animals treated with VitE+DL gained significant maternal LBW in 1st pregnancy, reduced dead kit number at birth and kit mortality rate at weaning, increased live kits and total kit weight at birth and weaning in the two pregnancies, and also increased significantly kit weight at birth and weaning in the treatments than controls in the two pregnancies, and DL was greater in 1st pregnancy. Progesterone concentrations in mid-pregnancy rose significantly in VitE+DL during 1st pregnancy and DL in 2nd pregnancy. Malondialdehyde concentrations dropped significantly in VitE and VitE+DL in mid-pregnancy in the two pregnancies. Eventually, the integration of VitE and DL displayed their unique properties for improving productive and reproductive performance in nulliparous rabbits.

An Integrative ATAC-Seq and RNA-Seq Analysis of the Endometrial Tissues of Meishan and Duroc Pigs.

Meishan pigs are a well-known indigenous pig breed in China characterized by a high fertility. Notably, the number of endometrial grands is significantly higher in Meishan pigs than Duroc pigs. The characteristics of the endometrial tissue are related to litter size. Therefore, we used the assay for transposase-accessible chromatin with sequencing (ATAC-seq) and RNA-sequencing (RNA-seq) to analyze the mechanisms underlying the differences in fecundity between the breeds. We detected the key transcription factors, including Double homeobox (Dux), Ladybird-like homeobox gene 2 (LBX2), and LIM homeobox 8 (Lhx8), with potentially pivotal roles in the regulation of the genes related to endometrial development. We identified the differentially expressed genes between the breeds, including SOX17, ANXA4, DLX3, DMRT1, FLNB, IRF6, CBFA2T2, TFCP2L1, EFNA5, SLIT2, and CYFIP2, with roles in epithelial cell differentiation, fertility, and ovulation. Interestingly, ANXA4, CBFA2T2, and TFCP2L1, which were upregulated in the Meishan pigs in the RNA-seq analysis, were identified again by the integration of the ATAC-seq and RNA-seq data. Moreover, we identified genes in the cancer or immune pathways, FoxO signaling, Wnt signaling, and phospholipase D signaling pathways. These ATAC-seq and RNA-seq analyses revealed the accessible chromatin and potential mechanisms underlying the differences in the endometrial tissues between the two types of pigs.

Effect of ewe birth litter size and estimation of genetic parameters on ewe reproductive life traits.

Ewe lifetime productivity has economic implications for producers because shorter lifetime productivity results in less profit. Productive years of ewes from extensive, range-based systems of the United States West are generally less than ewes from more temperate regions of the United States. Accordingly, ewes from range-based systems, especially those employing shed-lambing strategies, have been selected for increased litter size to offset decreased lifetime productivity. However, the relationship of the ewe's birth litter size (ELSB) has not been considered a potential contributor to lifetime productivity. Longevity (number of productive years, n = 1 per population) and stayability (probability to survive to the next age; ages 2-7 years, n = 6 per population) were investigated to understand ELSB effects on productive life. Columbia, Polypay, Rambouillet, and Targhee breeds were used in this study. Across-breed (n = 11 550) and within-breed (Columbia, n = 4 398; Polypay, n = 4 534; Rambouillet, n = 5 922; Targhee, n = 6 482) analyses were used. Depending on the population, records spanned from 1950 to 2008, where ewe's birth year was included as a fixed effect in the animal model using restricted maximum likelihood estimation procedures. Fixed effects investigated included ELSB (single-, twin-, or triplet-born) and ewe breed (across-breed analyses only). Regardless of trait or population used, heritability ranged from 0.06 ± 0.02 to 0.34 ± 0.03, where stayability at younger ages had the highest estimates. The breed effect was significant in all across-breed analyses (0.0001 ≤ P ≤ 0.038; n = 7), where Polypay, a breed selected for accelerated lambing and increased fertility, averaged shorter productive life or had a lower probability of survival to the next age compared with other breeds (longevity: 0.009 ≤ P ≤ 0.223; stayability: 0.000 ≤ P ≤ 0.842). The ELSB was significant in 60% (n = 5) and 37% (n = 30) of longevity and stayability analyses, respectively. Except for Targhee, all analyses showed ewes born in smaller litter sizes were associated with longer productive lives or higher probability of surviving to the next age, particularly in across-breed analyses (e.g., longevity: single- vs twin-born ewes, P = 0.004; vs triplet-born ewes, P = 0.003). This study provides evidence that increasing prolificacy in ewes from extensive, range-based production systems may impact productive life. Due to the low heritability of these traits, additional investigation into modeling these traits with dominance effects and litter size needs to be conducted.

Prevalence of lactational oestrus in cats and consequences for kittens.

OBJECTIVES: Although lactation and suckling suppresses fertility in most mammals, some feline breeders have reported spontaneous oestrus during lactation, causing distress to kittens. This led the Official French Feline Pedigree Registry (Livre Officiel des Origines Félines - LOOF) to send a questionnaire to cat breeders requesting data on their last three litters. The aim of this study was to investigate the prevalence of lactational oestrus, its impact on litters and potential associations with litter size, age, parity, breed and seasonality. METHODS: Answers from 108 breeders were collected, providing data on 238 litters in 23 different breeds. Data were also collected on successive litters from multiparous queens (n = 20) and were analysed separately from the 195 independent births. RESULTS: Of the 195 independent births with complete data sets, 96 (49%) queens came into oestrus during lactation, 37 (38%) of which were associated with loss of maternal interest (n = 20), milk quality variation (n = 2), clotted milk (n = 3), reduced milk quantity (n = 13), which in kittens led to reduced weight (n = 6), diarrhoea (n = 9), vomiting (n = 4), nausea (n = 2) or death (n = 4), and bottle feeding (n = 2), early weaning (n = 4) or modified litter behaviour (n = 1). A significant association was found between small litter size (one or two kittens) and the onset of lactational oestrus (P = 0.007) and between births occurring in February, March and April and lactational oestrus (P = 0.005); there was no association with age or breed. CONCLUSIONS AND RELEVANCE: Breeders perceived a relationship in 38% of cases of lactational oestrus with maternal disinterest, clotted milk, reduced milk yield and in kittens, weight loss, vomiting, diarrhoea or even death. An association between small litter size and lactational oestrus was found, as well as with births occurring between February and April. Breeders presenting with at-risk females should be warned. Conservative and preventive measures such as contraceptive options are discussed as a possible therapy.

The effect of placentation type, litter size, lactation and gestation length on cancer risk in mammals.

Reproduction is a central activity for all living organisms but is also associated with a diversity of costs that are detrimental for survival. Until recently, the cost of cancer as a selective force has been poorly considered. Considering 191 mammal species, we found cancer mortality was more likely to be detected in species having large, rather than low, litter sizes and long lactation lengths regardless of the placentation types. However, increasing litter size and gestation length are not per se associated with an enhanced cancer mortality risk. Contrary to basic theoretical expectations, the species with the highest cancer mortality were not those with the most invasive (i.e. haemochorial) placentation, but those with a moderately invasive (i.e. endotheliochorial) one. Overall, these results suggest that (i) high reproductive efforts favour oncogenic processes' dynamics, presumably because of trade-offs between allocation in reproduction effort and anti-cancer defences, (ii) cancer defence mechanisms in animals are most often adjusted to align reproductive lifespan, and (iii) malignant cells co-opt existing molecular and physiological pathways for placentation, but species with the most invasive placentation have also selected for potent barriers against lethal cancers. This work suggests that the logic of Peto's paradox seems to be applicable to other traits that promote tumorigenesis.

Genetic polymorphisms in ESR and FSHß genes and their association with litter traits in Large White pigs.

The estrogen receptor (ESR) gene and follicle-stimulating hormone ß (FSHß) gene are responsible for litter traits. The present study aimed to verify the polymorphisms of ESR and FSHß and assess their effects on the litter traits in 201 Large White pigs. Four SNPs (g.C669T, g.A1296G, g.C1665T and g.A1755G) were found in ESR. The TT genotype at g.C1665T locus and AA genotype at g.A1755G locus could significantly increase the total litter size of the first litter of American Large White pigs (p < 0.05). Eight SNPs were found in exon 3 of FSHß. The AA genotype at g.A511G locus, AA and AG genotypes at g.A617G locus, CC and CT genotypes at g.C630T locus, CT and TT genotypes at g.C652T locus, CT and TT genotypes at g.C735T locus, AA and AG genotypes at g.A746G, AA and AG genotypes at g.A921G and CT genotype at g.C678T could significantly increase the litter size of different strains of Large White pigs (p < 0.05). Our study revealed that the genetic variations of ESR and FSHß were closely related to the litter trait of Large White pigs. Therefore, ESR and FSHß genes could be used as molecular markers for the genetic selection of Large White pigs.

Piglets' behaviour and performance in relation to sow characteristics.

The importance of maternal care in commercial pig production is largely ignored. The sow has little possibility to interact with her piglets, and piglets are often subjected to early weaning or artificial rearing. This study aimed to investigate aspects of physiological and behavioural maternal provisioning that contribute to offspring outcomes. We hypothesised that better maternal care and nutritional provisioning would relate positively to piglet immunity, growth and behaviour. Nineteen sows and their litters were studied in free-farrowing pens. Oxytocin and tumour necrosis factor-α in colostrum/milk and salivary cortisol were sampled from sows throughout lactation. Sows were assessed for dominance rank, response to handling, maternal defensiveness, suckling initiation and termination, posture and sow-piglet contact. Piglets were weighed, measured for body mass index (BMI) and sampled for blood (Immunoglobulin G; at birth). After weaning, they experienced a human approach test (HAT) and novel object test. Correlations were explored between individual sow characteristics, individual piglet outcomes, and between sow characteristics and piglet outcomes averaged by litter. Significant correlations between sow and piglet factors were analysed at the litter level in mixed models with piglet outcomes as response variables and sow characteristics as predictor variables, while accounting for sow parity, litter size and batch. Litters grew faster when their sow had lower cortisol values (P = 0.03), while sows with lower cortisol levels had more successful suckling bouts and engaged in greater amounts of sow-piglet contact. Litters had a lower BMI at weaning when the sow had a higher milk fat percentage at d3. Litters of the most dominant sows took longer to approach the human in the HAT, while litters of sows with higher cortisol at d0 took longer to approach the novel object when assessed on correlations (r = 0.82, P < 0.001) but not when the model accounted for parity and litter size (P = 0.35). Only some of the measured nutritive and non-nutritive sow factors influenced litter performance and behaviour, with parity and litter size also playing a role. Given the continued increase in litter size, but also the interest in loose-housed lactation pens for sows, further research on sows' maternal investment and how it can be optimised is warranted.

Effects of exogenous GnRH administration on lambing performance of oestrus-synchronized Kazak ewes during the breeding season.

The objective of this study was to investigate the effects of GnRH at insemination on lambing performance of Kazak ewes. Oestrus was synchronized in 774 adult Kazak ewes using an intravaginal sponge impregnated with flurogestone acetate. The sponge was left in the vagina for 12 days followed with an injection of 330 IU of eCG at sponge removal. Each ewe was inseminated twice at 48 h and 60 h after sponge removal. The treatment group (n = 387) was intramuscularly injected at the first insemination with a dose of 25 µg GnRH and the control group (n = 387) with saline solution. The results showed that GnRH administration significantly decreased the fertility rate. In addition, significant differences were observed between the two groups in terms of the twin birth rate, the abortion rate and the litter size. In conclusion, GnRH administration at insemination was not recommended in Kazak ewes undergoing the fixed time artificial insemination during the breeding season. The breed may be a critical determinant of the potential for the exploitation of GnRH application in sheep breeding programmes.

A deletion mutation within the goat AKAP13 gene is significantly associated with litter size.

A-kinase anchoring protein 13 (AKAP13) is one of the AKAP protein family members, which is correlated with estrogen receptors (ERs) and progesterone receptor (PR) activity. Consequently, the AKAP13 gene is considered to be one of the candidate genes for regulating female fertility. Hence, the objectives of this study were to discover the potential insertion/deletion (indel) variants within the AKAP13 gene and evaluate their associations with litter size of Shaanbei white cashmere goats (SBWC) to screen candidate genes for the molecular marker-assisted selection (MAS). Ultimately, we found the 16-bp deletion of AKAP13 gene which displayed three genotypes (II, ID and DD). However, it was not confirmed to Hardy-Weinberg equilibrium (HWE) in the tested population. Statistical analysis demonstrated that this 16-bp indel locus was significantly associated with litter size in goats (p < 0.05), in which the ID genotype was a key genotype for increasing litter size in goats. Besides, independent χ2 tests between different genotypes and litter size showed that high-prolific groups had higher frequency of the 'D' allele (p < 0.05). Briefly, AKAP13 gene is a candidate gene for improving fertility, and its 16-bp indel locus can be used as a valid DNA molecular marker for the MAS in goat breeding.

Goat CLSTN2 gene: tissue expression profile, genetic variation, and its associations with litter size.

Calsyntenin-2 (CLSTN2) is involved in cell proliferation, differentiation, cell death, tumorigenesis, and follicular expression. Although CLSTN2 has been identified as a potential candidate gene for sheep prolificacy, no studies have been done on its effect on goat prolificacy. The purpose of this study was to identify mRNA expression and genetic variation within goat CLSTN2, and its association with prolificacy. Herein, we uncovered significant differences in mRNA levels of the CLSTN2 gene in different tissues in female goats (p < 0.01), including ovary tissue. Nine putative indels were designed to investigate their correlation to litter size, but only one 16-bp deletion was discovered in female Shaanbei white cashmere goats (n = 902). We discovered that a 16-bp deletion within the CLSTN2 gene was significantly correlated with first-born litter size (p = 0.0001). As shown by the chi-squared test, the genotypic II of single-lambs and multi-lambs was dramatically higher than with genotype ID (p = 0.005). Our findings suggest that indel within the CLSTN2 gene is a candidate gene affecting prolificacy in goats and may be used for Marker Assisted Selection (MAS) in goats.

Feline Fertility: Consequences of inbreeding and implications for reproductive fitness.

PRACTICAL RELEVANCE: When compared with the number of individuals that make up a dog breed, the population within a given cat breed is very small. Therefore, to maintain a breed standard, a certain degree of inbreeding is necessary. However, when inbreeding reaches a certain threshold, it can lead to decreased fertility, which manifests as failure to conceive, smaller litter size, increased neonatal illness and neonatal mortality. Breeders should be encouraged to keep comprehensive records on breeding outcomes, including number of kittens born, neonatal vitality, daily kitten weights and kitten health at weaning. Commercially available DNA panels are available to inform and facilitate excellent breeding choices and can estimate the coefficient of inbreeding. Clinicians should include a review of the degree of inbreeding in the work-up for any cattery or cat colony experiencing decreased fertility. AIM: The objective of this article is to provide clinicians, especially those working with cat breeders, with an easy-to-understand guide to genetics and to demonstrate how inbreeding influences fertility and neonatal survival. EQUIPMENT AND TECHNICAL SKILLS: Medical records and the pedigree of the cats in question are required to investigate cases of infertility that may be related to inbreeding. A DNA analysis kit that measures genetic diversity and health parameters can also be helpful; those that have been developed by geneticists and veterinarians at universities are preferable, as they include access to highly skilled genetic counselors and researchers who are open to working up newly discovered genetic diseases. EVIDENCE BASE: The material provided is based on current literature and the author's own studies examining outcomes in a closed cattery.

Effect of pre-conceptional nutrition and season on fetal growth during early pregnancy in sheep.

Gestational age in sheep can be closely predicted through ultrasonographic measurement of fetal bones when correlated to standardized fetal growth curves. However, these standardized curves do not account for factors that are known modulators of fetal growth, such as maternal nutrition or health status. Despite being seasonal breeders, and studies reporting an effect of season on birth weight, the influence of season on fetal growth has not been well characterized. In this study, we hypothesized that season of conception will affect fetal growth curves during mid-gestation and that pre-conceptional nutrition would have no effect. We investigated this by provisioning treatments of low, control, and high planes of nutrition during the lactation and flushing pre-conceptional periods to multiparous Dorset x Polypay and Dorset ewes over two seasons (the optimal breeding season [n = 97] and the suboptimal breeding season [n = 104]). Females were mated naturally with mating dates recorded, fetal biparietal diameter measured via ultrasound between gestational days 35-71, and newborn weights recorded at lambing. Pre-conceptional nutritional treatments did not affect fetal biparietal diameter. However, low vs. high nutrition in the pre-conceptional lactation (but not flushing) period resulted in reduced lamb birth weights (P < 0.001). Early fetal growth tended to be faster in the suboptimal breeding season than in the optimal breeding season (P < 0.061) with lambs being heavier at birth in the optimal breeding season (P < 0.001). There was no effect of fetal sex or litter size on fetal biparietal diameter during the first half of pregnancy, however both sex and litter size influenced lamb birth weight (P < 0.001) with males being heavier than females and singletons being heavier than twins and triplets. Mating date within the flushing period had a significant effect on lamb birth weight regardless of season and independent of treatment, with ewes that conceived later in the flushing period having heavier lambs at birth (P = 0.007). These findings suggest that pre-conceptional under- or overnutrition resulting in substantial changes in body condition does not affect fetal growth during the first half of pregnancy. However, the reduction in lamb birth weight indicates that pre-conceptional maternal nutrition during the previous lactation period may affect fetal growth later in pregnancy.

The influence of litter birth weight phenotype on embryonic and placental development at day 30 of gestation in multiparous purebred Large White sows.

The aim of this study was to understand the intrauterine biological processes associated with the low litter birth weight phenotype in pigs. Analyses were conducted on reproductive data from a purebred Large White maternal line to identify sows (>2 parities) with repeatable high or low litter birth weight phenotype (HLBWP or LLBWP). A total of 40 sows were selected (n = 20 HLBWP and n = 20 LLBWP) and bred with semen from purebred Large White boars of proven fertility. Sows were euthanized on day 28-30 of gestation (day 29.5 ± 0.6) and samples of placenta and embryos collected. Total number of embryos (TNE), embryonic weight (EW), embryonic viability, and crown-rump (CRL) measurements were recorded, along with the ovulation rate (OR) and allantochorionic fluid volume (AFV). No significant difference was detected (P > 0.05) in OR, TNE, and number of viable embryos on day 30 of gestation between the two groups. There was no significant difference in EW (LLBWP: 0.80 ± 0.05 g; HLBWP: 0.88 ± 0.04 g, P = 0.18) or CRL (LLBWP: 21.5 ± 0.7 mm; HLBWP: 21.9 ± 0.68 mm, P = 0.46). Placental development represented by the average AFV was significantly lower in the LLBWP compared to HLBWP (LLBWP: 131 ± 9.82 mL; HLBWP: 149 ± 9.39 mL, P = 0.03). In conclusion, placental development may be the main factor causing lower BW of entire litters in LLBWP sows.

The model of litter size reduction induces long-term disruption of the gut-brain axis: An explanation for the hyperphagia of Wistar rats of both sexes.

The gut microbiota affects the host's metabolic phenotype, impacting health and disease. The gut-brain axis unites the intestine with the centers of hunger and satiety, affecting the eating behavior. Deregulation of this axis can lead to obesity onset. Litter size reduction is a well-studied model for infant obesity because it causes overnutrition and programs for obesity. We hypothesize that animals raised in small litters (SL) have altered circuitry between the intestine and brain, causing hyperphagia. We investigated vagus nerve activity, the expression of c-Fos, brain-derived neurotrophic factor (BDNF), gastrointestinal (GI) hormone receptors, and content of bacterial phyla and short-chain fatty acids (SCFAs) in the feces of adult male and female Wistar rats overfed during lactation. On the 3rd day after birth, litter size was reduced to 3 pups/litter (SL males or SL females) until weaning. Controls had normal litter size (10 pups/litter: 5 males and 5 females). The rats were killed at 5 months of age. The male and female offspring were analyzed separately. The SL group of both sexes showed higher food consumption and body adiposity than the respective controls. SL animals presented dysbiosis (increased Firmicutes, decreased Bacteroidetes) and had increased vagus nerve activity. Only the SL males had decreased hypothalamic GLP-1 receptor expression, while only the SL females had lower acetate and propionate in the feces and higher CCK receptor expression in the hypothalamus. Thus, overfeeding during lactation differentially changes the gut-brain axis, contributing to hyperphagia of the offspring of both sexes.

Detection of the 23-bp nucleotide sequence mutation in retinoid acid receptor related orphan receptor alpha (RORA) gene and its effect on sheep litter size.

Retinoid acid receptor related orphan receptor alpha (RORA) transcribes steroid-related genes to regulate estrogen synthesis. As an important reproductive trait, litter size relates to estrogen synthesis. Therefore, it is important to investigate the association between RORA gene and sheep litter size. In this study, one 23-bp nucleotide sequence mutation was identified in intron 1 of RORA gene in 532 female Australian White Sheep. Moreover, the polymorphic information content (PIC) values of this locus was 0.219. The litter size of ID genotype was significantly better than II genotype and DD genotype in the second born litter size (p < 0.05). This loci was related to third born litter size and the ID is the dominant genotype (p < 0.05). The association between combined genotypes and average litter size showed that sheep with heterozygote (ID) genotypes had larger lamb than homozygous (DD and II) genotypes. To sum, this study provided theoretical references for the comprehensively research of the function of RORA gene and the breeding of Australian White Sheep. The 23-bp indel variants could be considered as molecular markers for the second and third born litter size of sheep for MAS breeding.

Folic acid supplementation during pregnancy modulates hepatic methyl metabolism and genes expression profile of neonatal lambs of different litter sizes.

Maternal folic acid (FA) plays an important role in the fetus development, but it is unknown the response of hepatic metabolism in the offspring from different litter sizes to maternal FA supplementation. In the present study, this was done by feeding the ewes with 0, 16 and 32 mg/(kg·DM) FA supplemented diet during pregnancy and analysing the hepatic one-carbon metabolism-related indices and gene expression in the neonatal lambs of different litter sizes (twins, TW; triplets, TR). Regardless of litter sizes, the concentrations of folate, methionine, S-adenosylmethionine and DNA methyltransferase increased significantly, but homocysteine and S-adenosylhomocysteine decreased in the liver of newborn lambs from ewes whose diet was supplemented with FA. In TW, maternal FA status has little effect on hepatic genes expression profile of newborn lambs, and no significant enriched pathway was found. However, DEG involved in cell proliferation such as CCNA2, CCNB2, CCNE2, CDK1 and BUB1 were significantly enriched when the ewes were supplemented with FA in TR groups. In addition, nucleotide synthesis-related genes such as POLD1, POLD2, MCM4 and MCM5 were enriched markedly in DNA replication and pyrimidine metabolism pathways in triplets when a higher FA ingestion [32 mg/(kg·DM)] was implemented in ewes. This finding demonstrated that the hepatic methyl metabolism in TW and TR newborn lambs was regulated by maternal FA status. The hepatic cell proliferation and nucleotide metabolism related genes in TR were more susceptible to maternal dietary FA supplementation during pregnancy.